Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.
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PMID:Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement. 1634 Oct 46

The Philadelphia chromosome (Ph) as a secondary cytogenetic abnormality is a rare event. It is observed mostly as an additional, late-appearing cytogenetic change during the evolution of acute leukemia and its presentation as a secondary change at the onset of disease is much rarer. We describe here a patient with acute myelogenous leukemia (AML) who had Ph as a secondary chromosome abnormality at diagnosis. Cytogenetic analysis showed an abnormal karyotype, 45,XY,inv(3)(q21q26),-7[4]/45,idem, t(9;22)(q34;q11.2). The p190 variety of BCR-ABL rearrangements was confirmed by a real-time reverse-transcriptase polymerase chain reaction using fluorescent probes. To our knowledge, the minor BCR-ABL fusion gene involving a secondary Ph superimposed on inv(3) and monosomy 7 has not been reported in AML at diagnosis. Along with the identification of more cases, it will be possible to understand the exact role of this secondary Ph in a multistep leukemogenesis.
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PMID:The Philadelphia chromosome as a secondary abnormality in inv(3)(q21q26) acute myeloid leukemia at diagnosis: confirmation of p190 BCR-ABL mRNA by real-time quantitative polymerase chain reaction. 1649 May 99

t(11;19)(q23;p13.3); is one of the common chromosomal translocations in acute leukemias involving MLL rearrangements. This translocation generates MLL/ENL fusion transcripts. In a study of acute leukemias, 148 patients were identified to have MLL rearrangements by Southern blot analysis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay, using primer sets covering the 2 previously described breakpoints at exons 2 and 7 of ENL detected 11 samples harboring MLL/ENL. complementary DNA panhandle PCR further identified 4 additional cases with novel breakpoints in ENL at exon 4 or 6. Sequencing analysis showed that all novel fusion transcripts were in-frame. The conventional cytogenetic analysis failed to detect t(11;19) in 6 of 13 cases. Of 15 patients with MLL/ENL, 7 had precursor B-cell acute lymphoblastic leukemia, 4 had T-cell acute lymphoblastic leukemia, and 4 had acute myeloid leukemia. The present study showed that PCR-based techniques are more sensitive than conventional karyotyping for detecting MLL/ENL fusions and an extra antisense primer at exon 6 of ENL should be included in RT-PCR assay to ensure complete detection of all MLL/ENL fusion transcripts.
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PMID:Analysis of acute leukemias with MLL/ENL fusion transcripts: identification of two novel breakpoints in ENL. 1714 26

A 18-year-old man was diagnosed with acute promyelocytic leukemia (APL). The conventional cytogenetic analysis revealed normal karyotype 46, XY, t(15; 17). Reverse transcriptase polymerase chain reaction (RTPCR) identified PML-RARa chimeric transcripts. Complete remission (CR) was attained with 3 induction courses of Ara-C, daunorubicin and all-trans retinoic acid (ATRA). Three years later the patient relapsed. The blasts in bone marrow aspirate at relapse had AML-M3 morphology, and RT-PCR was positive for PML-RARa transcripts. The patient was treated with ATRA and daunorubicin without success. Two months later the blasts in bone marrow aspirate showed AML-M2 morphology, the karyotype was 47, XY, +8 and RT-PCR revealed the presence of AML1-ETO transcripts and absence of PML-RARa transcripts. The patient attained second CR with 3 induction courses -a course with Ara-C and daunorubicin and 2 courses with idarubicin, Ara-C and etoposide.
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PMID:Clonal heterogeneity in a patient with acute promyelocytic leukemia. 1741 15

Here we report a rare chromosomal translocation, t(12;22)(p13;q11), which was detected in a 53-year-old female patient diagnosed as having minimally differentiated acute myeloid leukemia (AML-M0) according to the French-American-British classification criteria. Chromosome painting analysis with probes for chromosomes 12 and 22 confirmed the result of the conventional cytogenetic analysis. Reverse transcriptase polymerase chain reaction revealed the TEL-MN1 fusion transcript. Interestingly, she presented primary multidrug resistance and did not respond to several kinds of chemotherapy regimens. Moreover, she could not achieve remission after two doses of monotherapy with Mylotarg. Flow cytometry analysis detected high levels of expression of P-glycoprotein, multidrug-resistant-related protein, lung-related protein, and glutathione S-transferase pi in this case at presentation. As far as we know, this is the first report of t(12;22)(p13;q11) translocation involving TEL and MN1 genes in an AML-M0 patient.
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PMID:Minimally differentiated acute myeloid leukemia with t(12;22)(p13;q11) translocation showing primary multidrug resistance and expressing multiple multidrug-resistant proteins. 1747 96

EVI is a proto-oncogene that is activated in acute myeloid leukemia with chromosomal rearrangements that map to chromosome 3q26. We previously reported the clinicopathologic features of five cases of acute myeloid leukemia carrying t(3;8)(q26;q24). Using fluorescence in situ hybridization analysis, we demonstrate in the current study that the breakpoint on chromosome 3 is at EVI1/MDS1, and the breakpoint on chromosome 8 is just distal to the PVT1 oncogene homolog, a C-MYC activator in mice. The breakpoint on chromosome 8 was detected between the components of the LSI MYC dual-color break-apart rearrangement probe. Reverse-transcriptase polymerase chain reaction assay showed expression of EVI1 in all four cases analyzed, and DNA sequence analysis confirmed the findings. Reverse transcriptase polymerase chain reaction assay also demonstrated the expression of PVT1 and C-MYC in all four cases assessed. Western blot analysis detected EVI1 in one case analyzed. We conclude that the t(3;8)(q26;q24) results in deregulated EVI1 expression, similar to other balanced or unbalanced chromosomal translocations involving chromosome 3q26.
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PMID:Aberrant EVI1 expression in acute myeloid leukemias associated with the t(3;8)(q26;q24). 1769 89

A 5-year-old boy who initially presented with ALL and relapsed 4 months later with AML was found to have an add(19) in the leukemia cells. FISH revealed that the add(19) was really a cryptic t(l2;l9)(p13.3;p13.3) interrupting E2A (TCF3). Nucleotide sequences of cloned genomic fragments with the E2A rearrangements revealed that the der(12) contained E2A joined to an intron of the NOLI (p120) gene. Reverse transcriptase (RT)-PCR of patient lymphoblast RNA showed expression of in-frame fusion cDNAs consisting of most of NOL1 fused to the 3' portion of E2A that encoded part of the second transcriptional activation domain and the DNA binding and protein dimerization motifs. The reciprocal der(19) E2A genomic rearrangements included 5' regions of E2A joined to an intron of the ZNF384 (NMP4, CIZ) gene, located approximately 450 kb centromeric to NOL1 on chromosome 12. RT-PCR showed expression of in-frame E2A-ZNF384 fusion cDNAs. To our knowledge, this is the second report of a chromosome translocation in leukemia resulting in two different gene fusions. This is the first report of expression of E2A fusion protein that includes the DNA binding and protein dimerization domains due to a more proximal break in E2A compared to those described previously.
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PMID:E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia. 1818 22

Treatment of acute promyelocytic leukemia (APL) with a combination of anthracycline-based chemotherapy and all-trans retinoic acid (ATRA) leads to very high rates of complete remission and survival. There are only a limited number of publications on the development of therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia during follow-up of APL. Although drugs targeting at DNA-topoisomerase II characteristically induce translocations involving 11q23, this was seldom seen in patients treated for APL. We report on a patient initially diagnosed with APL. Response to therapy was monitored by fluorescence in situ hybridization (FISH) and reverse-transcriptase polymerase chain reaction for the PML-RARalpha rearrangement. Consecutive samples showed a swift and complete reduction of PML-RARalpha rearranged cells. Twenty months after diagnosis, however, conventional cytogenetics revealed a complex karyotype with a translocation involving 11q23 and loss of chromosomes 7q and Xq. FISH analysis with the MLL probe identified 2q37 (harboring the SEPT2 gene) as the translocation partner of chromosome 11. We consider the rather unique t(2;11)(q37;q23) as the primary event causing therapy-related MDS in our patient. This case stresses the importance of conventional karyotyping to be performed on a regular basis in all treated APL patients for the early detection of chromosomal aberrations that indicate the development of therapy-related MDS or acute myeloid leukemia.
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PMID:Translocation (2;11)(q37;q23) in therapy-related myelodysplastic syndrome after treatment for acute promyelocytic leukemia. 1820 42

The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reverse-transcriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival.
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PMID:The evaluation of hTERT mRNA expression in acute leukemia children and 2 years follow-up of 40 cases. 1829 58

Acute myeloid leukemia (AML) represents a heterogeneous group of leukemia entities that differ with regard to biology, clinical course, and prognosis. Over the past decades, it has been shown that most AML cases exhibit chromosomal aberrations, gene mutations, and disordered gene expression that alter normal gene function, thereby contributing to leukemic transformation. Especially, in cytogenetically normal AML (CN-AML) molecular genetic and gene expression analyses are becoming of increasing importance. In addition to the impact of gene mutations, including the MLL, FLT3, CEBPA, or NPM1 genes in CN-AML, recent analyses have provided evidence that altered gene expression might not only be of biological but also of prognostic relevance in CN-AML patients. Quantitative reverse-transcriptase polymerase chain reaction (Q-RT-PCR) and recent advances in genome-wide DNA microarray-based gene expression profiling (GEP) represent powerful tools for the systematic exploration of the molecular variation underlying the biologic and clinical heterogeneity of CN-AML. Ultimately, a better understanding of gene expression alterations and hence the molecular basis of the disease will contribute to a refined leukemia classification, which will include both previously known CN-AML subgroups and novel classes defined by distinct gene expression clusters with prognostic significance.
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PMID:Gene expression with prognostic implications in cytogenetically normal acute myeloid leukemia. 1869 86


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